Age-related acquisition of somatic mutations in hematopoietic stem cells leading to their clonal expansion gives rise to the preleukemic condition known as clonal hematopoiesis (CH). In addition to increasing the predisposition for hematological malignancies, CH is also associated with elevated risk for aging-associated disorders including cardiovascular disease, chronic liver disease, kidney disease, and others. Here, we aim to uncover a general molecular mechanism underlying CH-associated pathologies using CH-associated cardiac dysfunction as a paradigm. We modeled CH in mice by competitively transplanting whole bone marrow (WBM) cells deficient for Tet2, a frequently mutated CH gene, into irradiated WT recipient mice. Compared to mice transplanted with WT WBM, the Tet2-/- WBM recipients (“Tet2-CH” mice) exhibited cardiac dysfunction, as evidenced by an increased incidence of atrial fibrillation (AF) and reduced left ventricular ejection fraction, an indicator of heart failure. The Tet2-CH mice also had increased cardiac fibrosis and upregulation of the inflammasome signaling pathway, including the activation of Gasdermin D, the executor of pyroptosis. Remarkably, Gsdmd-/- recipient mice were protected from Tet2-CH-associated cardiac dysfunction and fibrosis. Identifying the mechanisms that promote tissue fibrosis and inflammation in the context of CH is of significant therapeutic interest. We considered that Tet2-/- cells may lead to deleterious factors in the circulation. Using a multiplex cytokine array, we identified factors whose levels were preferentially elevated in the Tet2-CH model. Next, we identified those factors whose secretion was abrogated in Gsdmd-/- mice (compared to WT), under LPS-induced inflammatory stress. Among the handful of cytokines that satisfied both these criteria, interleukin-11 (IL-11) appeared to be the most interesting candidate. IL-11 is a pleiotropic cytokine that is a master regulator of tissue fibrosis in organs such as the heart, liver, and kidneys. IL-11 is also upregulated with age and has recently emerged as a critical regulator of mammalian lifespan and health span. In addition to its upregulation in the Tet2-CH mouse model, serum IL-11 levels are elevated in aged WT mice and in a Dnmt3a-CH mouse model. This constellation of evidence encouraged us to determine whether abrogation of IL-11 signaling would mitigate CH-associated cardiac dysfunction. Indeed, administering an anti-IL-11 neutralizing antibody not only alleviated cardiac fibrosis but also ameliorated cardiac dysfunction in the Tet2-CH mouse model. We have elucidated that among all the major bone marrow cell types, only the stromal cells appreciably secrete IL-11, which they do in response to TGF-β produced by megakaryocytes. Furthermore, immunostaining of femur sections revealed that megakaryocyte numbers were elevated in the Tet2-CH mouse model suggesting a mechanism for the elevated serum IL-11 levels in Tet2-CH mice. To determine the impact of circulating IL-11 levels on the incidence of cardiac dysfunction in humans, we analyzed the UK Biobank. After excluding people with preexisting cardiovascular disease or missing values, we constructed 2 cohorts with non-overlapping participants: those with IL-11 measured by the Olink platform (n=45,617) and those with genetically predicted IL-11 levels (n=395,385). Stratification of participants in these cohorts into tertiles based on either their measured IL-11 levels or predicted IL-11 levels, respectively, revealed that those with elevated IL-11 levels were associated with a higher incidence of CH-associated AF, but not non-CH-associated AF. In conclusion, we developed a Tet2-CH mouse model that exhibits cardiac dysfunction and fibrosis, which can be reversed by ablating Gasdermin D. We identify IL-11 signaling as a novel driver of CH-associated cardiac dysfunction. Antibody blockade of IL-11 signaling ameliorates fibrosis and cardiac dysfunction. Analysis of UK Biobank data underscores the pathogenic role of IL-11 signaling in humans with CH. Due to its roles as a master regulator of tissue fibrosis and as an activator of inflammasome signaling, targeting IL-11 signaling could serve as an attractive therapeutic intervention for CH-associated pathologies.
With the concept of the gut-lung axis reinforced in recent years, emerging evidence has shown that intestinal homeostasis is vital for lung health. Nevertheless, the impacts of lung homeostasis on intestinal tracts and their mechanism are rarely studied. Our results showed that papain-induced asthmatic mice exhibited apparent colonic injuries compared with controls, including increased intestinal permeability, neutrophil and Th17 infiltration in the colonic lamina propria. Moreover, the intranasal administration of papain aggravated such colonic injuries in mice with dextran sulfate sodium-induced colitis, as evidenced by increased occult blood scores, shortened colon length, and accumulated neutrophils. The level of IL-17A was also higher in the serum of asthmatic mice than wild-type mice. Interestingly, the pathologic scores, the proportion of Th17 cells, and neutrophil infiltration in the colon were markedly reduced after IL-17A blocking. Similarly, longer length, lower pathologic scores, and fewer neutrophils were also observed in the colon of IL-17-deficient asthmatic mice. More importantly, we demonstrated that severe gastrointestinal symptoms could accompany clinical asthmatics. The frequencies of Th17 cells and the mRNA expression of IL-17A in the peripheral blood of these patients were significantly enhanced. Besides, the gastrointestinal symptom rating scale scores positively correlated with the frequencies of Th17 in asthmatics. These findings enlighten that IL-17A aggravates asthma-induced intestinal immune injury by promoting neutrophil trafficking, which facilitates the exploration of new potential biomarkers to treat asthma.
医学生的医德教育对社会和个人有着重要影响,义诊实践是当代医学生服务奉献精神的有形载体,同时也是医学生了解和接触临床的一个重要方式,是连接学校和社会的纽带.为深入了解医学生思想政治教育情况,更有效地开展医德养成教育,故以北京中医药大学为例,对医学生义诊实践情况进行调查.结果 显示:绝大多数学生对参加义诊活动的必要性表示认同,并通过义诊活动学有收获,通过对调研结果的分析,在义诊活动的开展过程中,虽然发现了一些有意义的成果,但还存在需要完善和改进的方面,应切实将思政教育贯穿于临床实践与课程学习的全过程中,为医学院校培养德才兼备的医学人才奠定基础.
首都国医名师武维屏教授谨遵《内经》及仲景所论,在中医整体观念及辨证论治指导下取诸家之长,审证求因、谨守病机、司外揣内,提出"外风始受于肺,内风始生于肝,外风引动内风是咳、喘、哮发作的中心环节"的学术思想,重视从风论治咳、喘、哮.基于跟师临床医案,进一步拓展和解析武老"外风始受于肺,内风始生于肝"的学术思想,总结其从风论治咳、喘、哮的临床经验,继承和推广名老中医学术思想.
近年来,中医在传染性非典型性肺炎(SARS)、甲型H1N1流感(甲流)等新型突发传染病的防治方面发挥了巨大的作用.新型冠状病毒肺炎(COVID-19)的流行,又给人类的健康及社会稳定带来新的威胁.结合SARS、甲流的防治经验和COVID-19现有病例资料及文献,该文从病因、五运六气、病证特点、辨证论治等方面,浅析3种疫病的异同.SARS病因属“热毒”,病机可见“热毒、瘀血、气阴两伤”,治疗以清热解毒祛邪为主;甲流属“寒疫”,病机为风寒疫毒挟湿,治则以扶阳顾津、解表散寒、化饮祛湿为主;COVID-19属“湿毒”,故病机为“湿、毒、虚、瘀、风”,治疗以宣肺祛湿透邪为主.结合中医对既往传染性疾病的认识和防治经验,以及中国临床COVID-19治愈患者资料,为全国人民深入了解和应对COVID-19提供策略,以期完善COVID-19防治方案,发挥中医药在突发公共卫生事件中的作用.
[目的]探析从风论治结缔组织病相关间质性肺疾病(connective tissue disease-associated interstitial lung disease,CTD-ILD)的辨证思路,以期提高临床疗效.[方法]基于风邪致病特点"风为百病之长,善行数变,有内外之分",结合古籍文献及现有文献资料,考究风邪致病源流,从风邪致病的角度分析CTD-1LD病因病机,研究风药的有效性,并探讨对CTD-ILD的论治.[结果]CTD-ILD的临床症状、病情发展与风邪特点相契合,风邪是CTD-ILD的重要致病因素,"外风犯肺"兼"内风伏肺"为疾病始动环节,内外风共同起病.疾病本质为虚,风与虚、痰、瘀、毒为病机演变的关键.临床和实验研究均证明风药治疗此病有效.病程可分为早、中、晚三期,进行分期论治,早期以疏风为主,中期以搜风为宜,晚期以息风为要,治疗时应针对病情急缓、病性虚实、正气强弱,有侧重地选用风药.[结论]"风邪致病"贯穿CTD-ILD整个病程,治疗应抓住早、中、晚三期风邪致病特点,根据虚、痰、疼、毒等辨证施用风药.
目的:基于数据挖掘技术探讨现代复方治疗非小细胞肺癌的用药规律,为临床用药提供参考.方法:选取2010年至2017年北京301医院治疗非小细胞肺癌(NSCLC)的中药复方,建立现代中药复方治疗NSCLC方剂数据库,并采用SPSS 22.0及SPSS Modeler14.2软件进行频数及频率分析、因子分析、关联分析等,进而对中药复方用药规律进行定量、定性分析并探讨其可能相关机制.结果:中药复方治疗肺癌复方231首,中药389种,高频中药135味,其中用药频次排名前5位的中药依次是川贝母、炒黄芩、生龙骨、茯神、半枝莲;在涉及的39类药物中清热解毒药、补气药居于前列;归经以肺经、脾经、胃经为主;四气以寒、温、平、微寒为主;五味以甘、苦、辛为主.因子分析最后提取了12个公因子,累积贡献率达65.595%,其中以补益气血、养阴清热散结、健脾理气化痰为主;通过聚类分析,提取了40常用得药对或药组;关联分析共得到63条关联规则,药对以茯苓→陈皮、炒白术→陈皮为常用,3味药组以生黄芪→炒白术、茯苓,生神曲→炒白术、茯苓,陈皮→炒白术、茯苓为常用.结论:肺癌主因癌毒阻滞,痰热互结,临床诊疗以扶正祛邪为基本原则,以祛邪宜清热解毒、为主,并兼顾正气,补益气血以培元扶正.
目的 分析和评估基于"课程思政"理念下的学生标准化病人(Student Standardized Patients,SSP)在中医内科学教学中的效果.方法 在北京中医药大学2016级本科生的中医内科学教学中,以传统教学模式为基础,联用SSP教学模式,通过分析学生的主观评价及客观成绩,探讨SSP对学生道德、品德、行为、技能等思政及专业方面的提高作用.结果 在考试成绩、思维能力、诊疗技能、自学能力及学习效率方面,SSP教学后的卓越中医学八年制较前均极显著性提高(P<0.01).在自信心、开放思想、四诊技巧及辩证思路方面,SSP教学后的中医实验班五年制较未SSP教学的八年制学生(卓越中医学八年制及中医儿科学八年制)明显提高(P<0.05).参加SSP培训后的学生的医患人际沟通能力、团队合作意识及临床基本知识掌握力得到了更大的提高.且参加SSP培训的学生的教学满意度较未参加SSP培训的高10.03%.结论 在基于"课程思政"理念下的SSP教学模式应用下,能更好地提高学生的学习成绩、自信心及学习主观能动性,增强医患沟通、诊疗技能等能力,潜移默化地培养医学生"患者至上"的职业意识.
Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are epidemic, contagious, sudden, and publicly harmful diseases. The whole-genome nucleotide identity of the pathogens causing the two diseases reached 79.5%. The mechanism and treatment of COVID-19 are still under investigation. Combining the experiences of SARS prevention and treatment in 2003, and the case data and literature of COVID-19, the similarities and differences between the two diseases in terms of causes, susceptible people, characteristics, dialectical mode, and treatment were analyzed. The two diseases are both plagues in terms of Chinese medicine. The cause of SARS was “heat poison,” and its pathogenesis was “heat poison, stasis, and qi and yin deficiency.” Therefore the treatment regimen was mainly to clear away heat, detoxicate, and expel evil. While the cause of COVID-19 was “wet poison,” and its pathogenesis was “wet, poison, heat, stasis, close, syncope, and yang collapse.” Hence the basic treatment strategy was to declare lung and remove dampness. Treatment of COVID-19 was clearing away evil qi as soon as possible, with the basic treatment regimen, which was declaring lung, removing dampness, and dispelling the evil. Combined with Traditional Chinese medicine's (TCM's) understanding and experience in SARS prevention and treatment, and Chinese clinical cured cases, we try to provide strategies for people all over the world to understand and respond to COVID-19, through the analysis and comparison. To improve COVID-19 prevention and treatment regimen and give full play to the advantages of TCM.
肺炎的共同诊断 不管是哪种肺炎,都有共同的诊断标准:①新近出现的咳嗽、咳痰或者原有的呼吸道症状加重,并出现脓性痰,伴或不伴胸痛;②发热;③肺实变体征和(或)闻及湿性啰音;④血象中白细胞> 10×109/升或<4× 109/升,伴或不伴细胞核左移;⑤影像学可见肺部片状、斑片状浸润性阴影或间质性改变,伴或不伴胸腔积液.
目的 探究蒌芩止嗽优化方对机体铜绿假单胞菌(PA)感染的免疫保护作用.方法 体外实验观察蒌芩止嗽优化方对左氧氟沙星透过PA成熟生物被膜(BF)的影响.体内实验观察其对PA感染大鼠肺部组织TNF-α、IFN-γ的影响,探究蒌芩止嗽优化方对炎症机体免疫失衡的调控.结果 体外,蒌芩止嗽优化方与氨溴索均可以协助左氧氟沙星透过PA成熟生物被膜.体内,西药组与中药组均可促进肺部细菌的清除,并且有助于减轻肺组织的病理损伤;中药组与模型组比较肺部的TNF-α水平明显降低(P<0.001),IFN-γ水平显著提高(P<0.001);西药组与模型组比较肺部的TNF-α水平明显降低(P<0.001),IFN-γ水平虽轻微提高,但差异无统计学意义;中药组与西药组比较肺部的TNF-α水平明显降低(P<0.001),IFN-γ水平显著提高(P<0.001).结论 蒌芩止嗽优化方体外可协助抗生素透过成熟生物被膜,其机制可能是通过纠正PA感染大鼠体内炎症免疫失衡,一方面加快了肺部细菌的清除及减轻肺部病理损伤,从而减轻机体炎症反应;另一方面增强机体对PA生物被膜感染的抵抗力,从而间接达到清除细菌的作用,它与氨溴索比较的优势可能亦在于可以提高机体免疫力,其深层作用机制尚有待进一步深入探讨.
[目的]基于数据挖掘技术探究中药古方治疗肺癌的用药规律.[方法]以中国方剂数据库为检索库,检索治疗肺积或息贲的中药方剂,建立中药古方治疗肺癌方剂数据库,并采用Excel、SPSS 22.0及SPSS Modeler 14.0软件进行频数及频率分析、聚类分析、关联分析,进而对中药古方用药规律进行定量、定性分析.[结果]中药古方治疗肺癌涉及方剂40首,中药110种,高频中药38味,甘草、人参、槟榔、木香等较为常用;温里药、补气药、理气药、止咳平喘药较常选用;核心药物聚类分析结果形成5个类别;经关联规则分析,支持度≥10%,得出药对关联规则21条,3味药配伍关联规则60条.[结论]中药古方治疗肺癌以扶正祛邪为主要治则,多采用温阳益气,滋阴养血结合清热、化痰、止咳、解表、行气活血等方法选取相应中药组方治疗.
2019年12月武汉新型冠状病毒感染疫情的迅速蔓延,已成为威胁人类的健康杀手,面对突发公共卫生问题,本文基于中医瘟疫理论,分析新型冠状病毒肺炎(NCP)病因为"湿毒",具有超强传染性及隐匿性,存在无症状传染者;人群普遍易感,具有人传人特点,临床症状不典型,病势进展存在预测困难等诸多不利因素.防治方面亦体现了三因制宜、攻补兼施及辨证论治原则.探究如何运用传统中医瘟疫理论,分析新发传染病,以期完善防治方案.这对于今后有效运用中医经典瘟疫理论应对可能再次爆发的其他公共卫生传染病,具有一定的理论及现实意义.
基于中医整体思想及“治未病·既病防变——培土生金”思想,本文对《金匮要略·肺萎》中虚寒、虚热肺萎的病证辨识、甘草干姜汤及麦门冬汤组方思路进行分析,探讨张仲景在中医肺萎治疗方面的“治未病·培土生金”临床运用,以冀为中医肺萎方面现代治疗提供新思路.
基于历代医家提出的"肺痹-体痹"整体观念,文章总结武维屏教授临证经验:间质性肺病(肺痹)常与关节、皮肤病变(体痹)相合,临床患者多病情复杂,症状纷繁多变,多以祛邪通络、宣降肺气、和解表里、调畅气机、通补兼施为立法治则.阐述肺痹和体痹之间的关系与治疗.
目的:研究生地对SD大鼠2型糖尿病并发症的预防效果.方法:通过7周高脂饲料及STZ腹腔注射诱导SD大鼠成糖尿病模型,除正常组外均予高脂饲料及对应的预防措施,21周后测量大鼠空腹血糖、24 h尿量及尿蛋白、脏器湿重指数及HE染色,IL-18等指标,分析各组大鼠心、肝、肾脏病变程度,探讨生地对糖尿病并发症是否有预防作用.结果:与模型组相比,生地干预后SD大鼠体重升高;空腹血糖、24 h尿量及尿蛋白显著降低(P<0.01);ALT较模型组下降(P<0.05);右肾和心脏湿重显著减轻(P<0.01);治疗组轻微肾小球肥大、基底膜增厚较模型组轻;治疗组心肌细胞轻度水肿,未见排列紊乱.结论:21周干预下,生地对2型糖尿病心、肝、肾病变有一定预防作用.
Objective To observe the effect of needle embedment on auricular Shenmen (TF4) 24 hours on cerebral blood flow and Infarction area by laser doppler technique.Methods 50% FeCl3 was used to induce the thrombosis occlusion model of middle cerebral artery.Needle embedment (24hours) was used to auricular Shenmen (TF4) in auricular needle group.Circle slice without needle was fixed on TF4 in sham-auricular needle group.Aspirin(60 mg/kg)was intragastric administration in drug group once a day.Regional cerebral blood flow (rCBF) was measured with Laser Doppler flowmeter.Nerve motor function was measured with Neurological deficit scores.Infarction area was measured by 2,3,5-triphenyltetrazolium chloride staining method.Results After 50% FeCl3 application,the cerebral blood flow decreased rapidly and decreased to 22% by 20 minutes.The model of cerebral thrombosis occlusion was successful.Compared with the model group,the rCBF in auricular needle group was raised to 174% in 20 min.Needle embedment on TF4 can improve the nerve motor function and reduce the infarction volume (34%),P<0.01.Aspirin and sham-auricular were also effective.The effect of sham-auricular was the worst.Conclusion Needle embedment on auricular TF4 can rapidly improve the cerebral blood flow after cerebral ischemia,thereby improving the nerve motor function and reducing the infarct volume,and the effect is better than oral aspirin and sham-auricular needle.
目前大学生做兼职是比较普遍的现象,做兼职既可得到一定的经济收入,又能增强社会实践能力,对于大学生进入社会开始独立生活是有利的。为了了解大学生的兼职情况,此次研究以北京中医药大学西校区大学生为研究对象,通过调查问卷的方式,对大学生兼职的情况进行调查与分析,总结出北京中医药大学西校区学生兼职的现状,并对学院和性别间的相关问题进行了比较,最后对学校的管理提出了意见和建议。